This invention relates to a method and apparatus for quantitative assessment of the condition of bones through measurement of spatial profiles of acoustic wave propagation parameters that are sensitive to the bone's material properties, structure, and cortical thickness.
Investigation of mechanical properties of bone and assessment of bone quality is important in view of osteoporosis and for evaluation of bone fracture risk. Osteoporosis presents a common public health problem, becoming increasingly dramatic as the population ages. It affects a large proportion of post-menopausal women and elderly individuals of both genders. Proper treatment can reverse or inhibit the osteoporosis from progressing. Secondary osteoporosis and osteopenia are factors inherent to a variety of metabolic and endocrine disorders that require monitoring during treatment of the primary disease.
Radiological densitometers, including dual-energy x-ray absorption (DEXA) and quantitative computed tomography (QCT) devices are widely used for evaluation of bone density and bone mass, which decrease due to bone resorption in osteoporosis. However, osteoporotic fracture risk cannot be reliably predicted by bone density alone without referring to bone mechanical status, which correlates poorly with radiographic bone density. Planar densitometers provide data on the apparent bone density but do not distinguish between contributions from cortical thickness, which broadly varies among individuals, and from true bone density, affected by porosity and the level of mineralization. Changes in micro-structural properties, such as accumulation of micro-damages, are also associated with bone hardness and brittleness. These are yet other factors of bone fracture risk not assessable by DEXA or QCT. Besides those mentioned above there are many other reasons including high cost, lack of portability, and hazardous radiation exposure that altogether limit availability of this technique, encumbering its use in wider screening and monitoring of the at-risk population.
Quantitative ultrasound (QUS) presents an alternative to X-ray densitometry, possessing several advantages such as:                1) providing information on the elastic properties and structural changes (porosity) of bone, which is not assessable by DEXA;        2) posing no irradiation hazard, allowing radiation-safe and off-repeated measurements;        3) allowing portability, ease of use and lower costs.        
Ultrasound velocity directly depends on the bulk elasticity modulus of bone. Ultrasound attenuation, which is another important QUS parameter, reflects structural changes during osteoporosis as manifested by a decrease of trabecular density.
It is known that osteoporosis and osteopenia result in degradation of bone quality. There are two major contributors to poor bone quality:                1) factors that determine quality of the bone material, such as increased porosity, changes in mineralization, accumulation of micro-damages, etc. and        2) internal resorption dominating over bone remodeling, which ultimately leads to bone thinning.        
Osteoporosis fracture risk is caused by both of these factors acting separately or together causing worsening of mechanical characteristics and durability of bones. In long bones, increased progress of resorption takes place mainly from the endosteal surface expanding towards the periosteum, therefore causing trabecularization of inner layers of the compact bone and a decrease in the effective thickness of the cortex. Ultrasonic waves applied to the bone in axial propagation mode at a frequency of about 1 MHz are typically used for the assessment of material properties related to mineralization and porosity developing within the cortex (see for example Bossy E, Talmant M, Peyrin F, Akrout L, Cloetens P, Laugier P. An in-vitro study of the ultrasonic axial transmission technique at 1 MHz velocity measurements demonstrated sensitivity to both mineralization and intracortical porosity. J Bone Miner Res. 2004; 19(9): 1548-56). Assessment of cortical thickness is possible by application of guided waves in a lower frequency band, in which velocity is a function of the ratio of thickness to wavelength (see for example Lee K I, Yoon S W. Feasibility of bone assessment with leaky Lamb waves in bone phantoms and a bovine tibia. J Acoust Soc Am. 2004; 115(6):3210-7).
Another approach uses a pulse-echo mode and autocorrelation analysis of the signals reflected from inner and outer surfaces of the cortex (Wear K A. Autocorrelation and cepstral methods for measurement of tibial cortical thickness, IEEE Trans Ultrason Ferroelectr Freq Control. 2003; 50(6):655-60). Guided acoustic waves have been demonstrated to be informative about the biomechanical properties of bones in vitro, detecting manifestations of osteopenia in model studies on phantoms (Tatarinov A, Sarvazyan A. Dual-frequency method for ultrasonic assessment of bones: model study. Proc. World Congr. Ultrasonics, WCU 2003, Paris, 895-898) and discriminating osteoporosis patients with higher resolution when compared with the use of longitudinal acoustic waves (Nicholson P H, Moilanen P, Karkkainen T, Timonen J, Cheng S. Guided ultrasonic waves in long bones: modeling, experiment and in vivo application. Physiol Meas. 2002; 23(4):755-68).
A number of U.S. patents disclose through transmission ultrasonometers, generally applied to the bilaterally accessible bones such as a heel. U.S. Pat. No. 3,847,141 for example describes an ultrasonometer, which measures ultrasound propagation parameters by transmitting and receiving an acoustic signal using narrowband transducers positioned at the opposite sides of a bone. Systems disclosed in U.S. Pat. Nos. 4,421,119, 4,474,959, 4,913,157, 4,926,870, 4,930,511, 4,941,474, and 5,592,943 operate with ultrasonic longitudinal waves in broadband range and in the analysis of recorded acoustic signals. These systems make use of both the changes in the ultrasonic spectra and in the temporal propagation parameters. The systems differ by the manner of acoustic coupling of the transducers to the patient's body, calibration procedures and data processing algorithms. U.S. Pat. Nos. 5,840,029 and 6,086,538 describe ultrasonometers providing measurements at a number of spatially separated locations on the bone to identify a region of interest thereon.
Other known ultrasonic techniques for characterization of bones include measurements of ultrasound reflection from the bone at various angles of incidence as described for example in U.S. Pat. No. 5,038,787. Another known system determines attenuation from reflected signals as described in U.S. Pat. No. 6,328,695. Another yet example of such system combines a non-linear analysis and evaluation of shear wave propagation parameters, as described in U.S. Patent Application No. 20020161300. For more sensitive assessment of osteoporosis and bone fracture risk, some authors combine ultrasonic, densitometric and other data, as described in U.S. Pat. Nos. 6,029,078, and 6,740,041.
Assessment of bone by unilateral measuring the velocity of ultrasonic waves traveling along the bone is described in U.S. Pat. Nos. 5,143,072 and 6,328,695. In U.S. Pat. No. 5,143,072 a system is proposed that has two receivers positioned co-linearly to measure the propagation velocity by time increment between the receivers, therefore eliminating the error caused by delay of the sound pulse in soft tissue. In U.S. Pat. No. 6,328,695, the error of ultrasound velocity in bone measurement due to the presence of soft tissue layer is accounted for by making separate pulse-echo measurements of the ultrasound delay in the soft tissue layer. In both cases, a longitudinal ultrasonic wave is used, the velocity of which is a function mainly of the bone material elasticity modulus.
Application of guided stress waves for evaluation of the bone firmness is described in U.S. Pat. No. 5,882,303. The guided waves are generated by hammering impacts. The transmission function referring to pulse width and height is acquired at a number of set points along the bone. Being potentially good indicators of the total bone rigidity determined by both the bone geometry and material stiffness, these parameters do not discern between the above mentioned factors and, besides, could be influenced by numerous random factors such as individual anatomical variations.
A method and device for multi-parametric ultrasonic assessment of bone conditions are proposed in U.S. Pat. No. 6,468,215, where combined application of the longitudinal wave and quasi-flexural mode of guided waves is described. The patent also describes the stepped scanning procedure along the bone trajectory and presentation of measured ultrasonic parameters as axial profiles. The axial profiles can serve as a measure of spatially developing processes in bones and individual characteristics of these processes among patients. However, the method and the device described in U.S. Pat. No. 6,468,215 have the following major shortcomings:                1) Excitation of different wave modes is achieved using the first and third harmonics of a resonant piezoelectric transducer. Generation and receiving of ultrasound waves by such resonant narrow band transducers does not allow making measurements with short ultrasonic pulses. When the received pulse is long, it requires a much longer distance between the transmitter and the receiver to have the arrival of different modes of acoustic waves separated in time. It is hard to realize sufficiently long acoustic base because of anatomical limitations and significant attenuations of ultrasonic waves in bone. Use of narrow band transducers does not allow flexibility in varying the carrier frequency of ultrasonic waves, which is necessary for obtaining data on propagation parameters of various modes of acoustic waves in the bone;        2) Only a fraction of diagnostically relevant information that is present in the received ultrasonic waveforms is analyzed. Although ultrasound propagation parameters, such as velocity, attenuation, and their frequency dependences are informative characteristics, the calculation of these parameters is based on numerous poorly based assumptions. This can be avoided if the diagnostic information is directly extracted from the received acoustic waveforms, which is not envisioned in the method described in the patent.        
The need therefore exists for an improved device, data acquisition, and processing methods for the axial testing of long bones and development of additional parameters for sensitive assessment of bone conditions.